SUBA-Itraconazole Therapy for Coccidioidomycosis Refractory or Intolerant to Fluconazole

NCT04809649 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 1666482
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine how safe, effective, and well tolerated a new investigational antifungal drug, SUBA-itraconazole, is for patients who have been previously treated with fluconazole and have had either an insufficient response to treatment with fluconazole or a negative reaction to fluconazole preventing their further treatment with it.

Conditions

Coccidioidomycosis; Valley Fever

Outcome Measures

Primary Outcomes (1)

• 1. The Proportion of Participants Who Achieve Clinical Improvement, in All Participants Who Took at Least One Dose of Study Drug

  Clinical Improvement is defined as at a) at least a 50% reduction in coccidioidomycosis Mycoses Study Group (MSG Score) from baseline value, or b) the unequivocal documentation of clinical improvement as recorded on the progress note of the medical provider, or c) a 25%-49% decrease in the MSG score from baseline value and a physician's impression of improvement as recorded on the progress note. The MSG score is a composite scoring system that has been used in numerous past studies of coccidioidomycosis. This system comprises the sum of points assigned based on the findings of: (1) clinical assessments, (2) radiographic imaging, and (3) serologic assays, with a lower score indicating better health.

  180 days

Secondary Outcomes (7)

• Number of Participants with Treatment-Emergent Adverse Events

  180 days

• Number of Participants with Abnormal Laboratory Evaluations of Safety

  180 days

• Number of Participant Discontinuations of Therapy Due to Treatment-Emergent Adverse Events and/or Laboratory Evaluations of Safety

  180 days

• Number of Participants with Any Interruptions of Therapy due to Treatment-Emergent Adverse Events and/or Abnormal Laboratory Evaluations of Safety

  180 days

• Number of Participants with Interruptions of Therapy 7 Days or More in Duration due to Treatment-Emergent Adverse Events and/or Abnormal Laboratory Evaluations of Safety

  180 days

Study Arms (1)

SUBA-itraconazole

EXPERIMENTAL

Drug: SUBA-itraconazole Dosage Form: 65 mg capsules Dosage: 260 mg/day Frequency: 130 mg twice daily (BID) Duration: Up to 180 days

Drug: SUBA-itraconazole

Interventions

SUBA-itraconazole DRUG

Participant will receive treatment with SUBA-itraconazole

Also known as: Tolsura

SUBA-itraconazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects ≥ 18 years who have given written informed consent to participate
• Subjects with a proven or probable coccidioidomycosis according to current European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, including subjects who:
• Are immunosuppressed, including as a result of HIV/AIDS
• Have had a heart, lung or bone marrow transplant
• Have had chemotherapy for cancer
• Are otherwise not immunocompromised
• Refractory for ≥ 40 days, or intolerant to fluconazole treatment for coccidioidomycosis in the opinion of the investigator
• Refractory disease defined as failure to obtain an adequate therapeutic response after ≥40 days of therapy:
• Lack of improvement in signs, symptoms or imaging findings OR
• Continued isolate of Coccidioides or histopathologic findings of • Coccidioides despite antifungal therapy
• Rising Complement Fixation Titers
• Progression of disease (requires worsening of attributable signs, symptoms or imaging, or a new site of infection
• Intolerance defined as adverse events attributable to fluconazole therapy defined as organ toxicity of grade 3 or higher, nephrotoxicity (Creatinine twice the upper limit of normal), or idiosyncratic reactions therapy that in the opinion of the investigator may be relieved by a therapeutic change OR refusal of the patient to take further fluconazole
• Subjects of childbearing potential should be non-pregnant and not breastfeeding (and not planning to become pregnant)
• Postmenopausal for ≥1 year

You may not qualify if:

• Significant liver dysfunction as evidenced by total bilirubin \> 1.5 × the upper limit of normal (ULN) range unless considered due to Gilbert syndrome, in which case \> 3 × the ULN, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels \> 1.5 x the ULN.
• Evidence of CNS infection.
• Unable to take PO medications.
• Documented intolerance, allergy or hypersensitivity to itraconazole.
• Inability to comply with study treatment, study visits, and study procedures.
• Known history or presence of congestive cardiac failure, fungal endocarditis, or other causes of ventricular dysfunction that may outweigh the benefit of itraconazole.
• Subjects with active tuberculosis.
• Concurrent use of drugs that effect SUBA™-itraconazole concentrations
• Subjects who washout from prohibited medications can be included
• Any known or suspected condition of the subject that may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy.
• Treatment with any investigational agent in the 30 days prior to study entry.
• Subjects unlikely to survive 30 days based on the opinion of the investigator.
• Subjects with body weight \< 40 kg.

Sponsors & Collaborators

• George R Thompson: lead
• Mayne Pharma International Pty Ltd: collaborator

Study Sites (1)

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Coccidioidomycosis

Interventions

Itraconazole

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• George R Thompson, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 22, 2021
• Study Start: May 15, 2021
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: July 19, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)